Method for determining relatedness of genomic samples using partial sequence information

Abstract

Disclosed are methods for testing biological samples containing genomic nucleic acids obtained from an organism having a genome, such as a human genome. It is often desirable to analyze a DNA sample or more than one, different DNA samples, to determine whether the sample comes from one individual or two individuals. The present method requires very low amounts of DNA and can use partial sequences of DNA fragments. Partial sequences are analyzed for the presence of polymorphisms (e.g. SNP's) that can be mapped to a reference SNP map. The distance between similar SNPS, which are genetically linked, can be used to statistically determine a likelihood of identity of individuality in a sample.

What is claimed is: 
     
       1. A method for determining whether a first human genomic sample and a second human genomic sample are from the same individual, comprising:
 (a) obtaining, by massively parallel sequencing, a plurality of nucleotide sequence reads from a first human genomic sample and a second human genomic sample, wherein the sequencing is performed at a coverage of 0.5% or greater of the genome of the first human genomic sample and the genome of the second human genomic sample, mapping the sequence reads to a chromosome or genome, thereby generating mapped reads, and observing alleles at hundreds of thousands or more polymorphic sites in the mapped reads, thereby determining mapped polymorphisms; 
 (b) obtaining linkage disequilibrium (LD) log-likelihood ratios (LLRs) for pairs of the mapped polymorphisms determined in step (a), wherein each pair comprises a polymorphism in the first genomic sample and a polymorphism in the second genomic sample, and wherein the LLRs reflect the likelihood that the mapped polymorphisms determined in step (a) derive from the same individual or different individuals; and 
 (c) determining an aggregate likelihood that the first genomic sample and the second genomic sample are from the same individual by summation of LLRs obtained in step (b). 
 
     
     
       2. The method of  claim 1  wherein said aggregate likelihood is determined using LD information from a SNP database. 
     
     
       3. The method of  claim 1  wherein SNP linkage information is obtained from a database containing a listing of SNP sequences, genotypes, and locations across a genome. 
     
     
       4. The method of  claim 1 , wherein the first genomic sample and the second genomic sample are independently selected from the group consisting of: a blood sample, a hair sample, a hair root sample, a saliva sample, a semen sample, a bone marrow sample, and combinations thereof. 
     
     
       5. The method of  claim 1 , wherein the mapped polymorphisms in step (a) are selected from the group consisting of variable number tandem repeats (VNTRs), simple-tandem repeats, short tandem repeats (STRs), single nucleotide polymorphisms (SNPs), and human mitochondrial DNA (mtDNA) first hypervariable region (HVI) and second hypervariable region (HVII). 
     
     
       6. The method of  claim 1 , wherein the mapped polymorphisms in step (a) are SNPs. 
     
     
       7. The method of  claim 6 , wherein said SNPs are recorded in a publicly available archive containing chromosomal locations of SNPs within the archive. 
     
     
       8. The method of  claim 6 , wherein said SNPs occur in unique subsequences within a genome. 
     
     
       9. The method of  claim 6 , wherein said SNPs occur in at least one percent of a population. 
     
     
       10. The method of  claim 1 , wherein the massively parallel sequencing generates read lengths between 50 bp and 350 bp. 
     
     
       11. The method of  claim 10 , wherein said sequencing comprises a step of randomly fragmenting genomic DNA in a sample. 
     
     
       12. The method of  claim 1 , wherein the sequencing is performed at a coverage between 1% and 10% of the genome of the first genomic sample and the genome of the second genomic sample. 
     
     
       13. The method of  claim 1 , wherein obtaining LD LLRs comprises sliding windows of polymorphisms located in proximity on a chromosome. 
     
     
       14. The method of  claim 1  wherein said LD LLRs are determined using LD information from a polymorphism database. 
     
     
       15. The method of  claim 1 , wherein step (a) comprises observing alleles at millions of polymorphic sites in the mapped reads. 
     
     
       16. The method of  claim 1 , wherein step (b) further comprises comparing the mapped polymorphisms determined in step (a) with a reference set of mapped polymorphisms. 
     
     
       17. The method of  claim 16 , wherein the reference set of mapped polymorphisms are SNPs. 
     
     
       18. The method of  claim 17 , wherein the reference set of mapped polymorphisms comprises millions of SNPs. 
     
     
       19. The method of  claim 17 , wherein the reference set of mapped polymorphisms comprises 90 million SNPs.